COLLABORATIVE RESEARCH PROJECT 2 (ENVIRONMENTAL AND GENETIC DETERMINANTS OF PUBERTY). Female puberty is a time at which dramatic morphological and physiological changes in mammary gland development occur in the growing girl. While early age of menarche has long been known to increase breast cancer risk, little is known about associations with other measures of puberty. Biologically, in-utero exposures and early childhood events, including onset of thelarche, may be more important predictors of breast cancer risk than menarche. The study we propose takes advantage of a unique multiethnic cohort of 500 girls, ages 4-11, for whom we have extensive information on in-utero exposures and birth characteristics. The project has three inter-linking tiers of data collection/analysis: (1) an already available comprehensive data set on the in-utero and birth periods; (2) a longitudinal follow-up study with multiple assessments from age 4-11 to be performed under the budgeted grant and (3) a plan for further investigations of collected data (e.g. genetic and blood assays) to be executed in all girls with supplementary funding to be sought in the future. The girls we will study are the daughters of women enrolled in an NIH-supported study of the etiology of preterm delivery conducted in 5 cities in Michigan. That study enrolls women during pregnancy and obtains biological specimens (serum, vaginal fluid, hair, saliva, placenta), blood pressure, biomedical information (pregnancy disorders, gestational age, birth measures) and a detailed assessment of stress, psychological state and social circumstances. To this already collected information on the mothers of our cohort, we will add prospective monitoring of pubertal development at six-month intervals between ages 4 and 11, supplemented by physical assessments of puberty by trained health professionals annually between ages 7-11. We will examine prenatal exposures, birth characteristics, environmental exposures, diet and nutrition, growth and changes in body composition, physical activity, social and psychological stress in the child and her family, and genetic polymorphisms for their relationship to thelarche, pubarche,menarche and growth at several points in childhood. Exposures of environmental contaminants will be obtained by multiple approaches, including interviews to estimate pesticide exposure and via measurements on 24-hour urine collections at age 4. In a nested case-control pilot study of girls with early onset of thelarche (age 7) and later (age 10), we will also assay for hormonal changes in the collected blood and urine samples. The assembled data base will provide us with the material necessary to develop a model that relates timing of pubertal development in girls to a complex interrelationship of the hormonal milieu, anthropometric measures and onset of secondary sex characteristics, each of which can be influenced by environmental exposures occurring in-utero through childhood with the individual's inherited genetic polymorphisms potentially modifying the effect of these exposures on timing of pubertal development.